Backgroundc-Met has been shown to promote organ development and cancer progression in many cancers. However, clinicopathological and prognostic value of c-Met in breast cancer remains elusive.MethodsPubMed and EMBASE databases were searched for eligible studies. Correlation of c-Met overexpression with survival data and clinicopathological features was analyzed by using hazard ratio (HR) or odds ratio (OR) and fixed-effect or random-effect model according to heterogeneity. All statistical tests were two-sided.Results32 studies with 8281 patients were analyzed in total. The c-Met overexpression was related to poor OS (overall survival) (HR=1.65 (1.328, 2.051)) of 18 studies with 4751 patients and poor RFS/DFS (relapse/disease free survival) (HR=1.53 (1.20, 1.95)) of 12 studies with 3598 patients. Subgroup analysis according to data source/methods/ethnicity showed c-Met overexpression was related to worse OS and RFS/DFS in Given by author group, all methods group and non-Asian group respectively. Besides, c-Met overexpression was associated with large tumor size, high histologic grade and metastasis.ConclusionsOur results showed that c-Met overexpression was connected with poor survival rates and malignant activities of cancer, including proliferation, migration and invasion, which highlighted the potential of c-Met as significant candidate biomarker to identify patients with breast cancer at high risk of tumor death.

BACKGROUND:Inhibition of lymphocytes infiltration and activity may impair antitumor immune response and limit treatment responsiveness. Wnt/β-catenin pathway has been suggested to contribute to immune evasion in tumor by suppressing the function of immune cells and excluding T cell infiltration. However, the effects of Wnt/β-catenin on TILs recruitment remain controversial.OBJECTIVE:We aimed to investigate whether intratumoral Wnt/β-catenin signaling could affect the lymphocyte infiltration in breast cancer.METHODS: The distribution of stromal TILs, CD8+ and FOXP3+ TIL subsets, and the expression of β-catenin were separately assessed on consecutive sections of 96 breast cancer specimens.RESULTS: Both stromal infiltrated TILs and β-catenin expression were upregulated in hormone receptor negative HER2-enriched and TNBC subtypes. Furthermore, high levels of stromal TILs as well as CD8+ or FOXP3+ TIL subsets were associated with β-catenin overexpression by breast cancer, respectively.CONCLUSIONS: For the first time, we demonstrated that rather than excluding lymphocytes infiltration as reported in mela-noma, high levels of TILs were associated with β-catenin overexpression in BC. Wnt/β-catenin signaling may play a critical role in BC immunity, particularly in HER2-enriched and triple negative BC, and may serve as a potential target for regulating immune infiltrates in breast cancer.